Despite consistent evidence linking smoking cessation pharmacotherapy adherence to better outcomes, knowledge about objective adherence measures is lacking and little attention is given to monitoring pharmacotherapy use in smoking cessation clinical trials.To examine unannounced telephone pill counts as a method for assessing adherence to smoking cessation pharmacotherapy.Secondary data analysis of a randomized pilot study.46 moderate-to-heavy (>10 cigarettes per day) African-American smokers.Smokers received 1 month of varenicline (Pfizer Global Pharmaceuticals, New York, NY) in a pill box at baseline. Unannounced pill counts were completed by telephone 4 days prior to an in-person pill count conducted at Month 1. At both counts, each compartment of the pill box was opened and the number of remaining pills was recorded.Participants were a mean age of 48 years (SD = 13), predominately female (59%), low income (60% < $1800 monthly family income), and smoked an average of 17 (SD = 7) cigarettes per day. A high degree of concordance was observed between the number of pills counted by phone and in-person (r(s) = 0.94, P < 0.001). Participants with discordant counts (n = 7) had lower varenicline adherence (mean [SD] = 77% [18%] vs 95% [9%], P < 0.0005), but reported better medication adherence in the past (1.0 [0.8] vs 2.8 [1.0], P < 0.0004) than participants with matching phone and in-person counts (n = 39).Unannounced telephone pill counts appear to be a reliable and practical method for measuring adherence to smoking cessation pharmacotherapy.